Liver X receptors (LXRs), members of the nuclear receptor super-family, include LXRα and Ubiquitous Receptor (UR, also called LXRβ). They transactivate gene expression. Several cholesterol homeostasis-related genes have been identified as LXR direct targets, e.g., those coding for cholesterol efflux transporter ATP-binding cassette 1 ABCA1 and ABCG1, cholesterol 7α-hydroxylase (the rate-limiting enzyme for bile acid synthesis from cholesterol), cholesteryl ester transfer protein (CETP), lipoprotein Apolipoprotein E (ApoE), and sterol regulatory element-binding protein 1c (SREBP-1c). See, e.g., Schwartz et al., Biochem. Biophys. Res. Commun., 2000, 274: 794-802; Laffitte et al., Proc. Natl. Acad. Sci. USA, 2001, 98(2): 507-512; and Repa et al., Genes Dev., 2000, 14: 2819-30.
Regulation of these genes by LXRs affects cholesterol reverse transport and disposal, which in term has a direct impact on the formation of lipids and fibrous elements, expression of ApoE gene, and activation of nuclear factors kappa-B and AP-1. Accumulation of lipids and fibrous elements in arteries results in atherosclerosis, the underlying cause of various diseases such as heart disease and stroke. Deficiency of ApoE gene expression has been found related to diseases such as Alzheimer's disease. Activation of nuclear factors kappa-B and AP-1 modulates the human immune system and enhance its anti-inflammatory abilities.